Phase I/II Clinical Trial of AMT-130

uniQure has initiated the first gene therapy clinical trial in Huntington’s disease.

The clinical trial uniQure is conducting in HD uses a gene therapy known as AMT-130. This investigational treatment is the first one-time administered gene therapy to enter clinical testing for the treatment of HD. AMT-130 is administered once by neurosurgical procedure. There are two key components to AMT-130: a vector and a gene encoding a microRNA (miRNA). The vector acts as a delivery system and is based on a non-disease causing adeno-associated virus (AAV) that has been changed to carry and deliver a gene encoding a miRNA that will recognize, bind and non-selectively lower the human huntingtin protein. miRNA are small pieces of genetic material that can prevent production of a given protein. To non-selectively lower” human huntingtin protein means that production of both the disease-causing mutant (mHTT) and normal huntingtin protein (HTT) will be decreased.

Under our U.S.-based protocol, we have completed enrollment of both the low-dose and high-dose cohorts (n=26) of the trial. We recently added a third cohort (n=18) that will explore an alternative surgical administration of AMT-130.

Animated illustration of how AMT-130 is administered into the caudate and striatum regions of the brain via a micro-catheter

Below are answers to some frequently asked questions about the trial. For additional information, please speak with your doctor or contact us using the link below.

  • Why is this study being done?

    This is the first study testing AMT-130 in humans. The main purpose of this study is to find a safe dose of AMT-130 in adults who have tested positive for the HD gene and who have early-stage HD. The study will also look at how the body processes AMT-130 and will explore how AMT-130 might affect how the disease progresses. The therapeutic goal is to inhibit the production of the mHTT by using AAV to deliver genes encoding miRNA directly to the brain for non-selective (both mutant and normal) lowering of the huntingtin protein.

  • Who is eligible for the study?

    The inclusion criteria require, but are not limited to:

    • Patients with a definitive clinical diagnosis of early manifest HD
    • Males and females, between the ages of 25 to 65 years old
    • CAG repeat expression of ≥40

    Please note that participants will need to be off any other experimental agents for 60 days prior to screening. Previous exposure to gene therapy, huntingtin lowering strategies, or experimental brain surgery are prohibitive to study participation.

    The most important step in determining eligibility is to speak to a physician at one of the clinical sites. One should always talk to their own doctor as well when making any major medical decisions.

  • What is involved in the study?

    It is important to reiterate that AMT-130 is administered only once. So far the study has tested two dose levels of AMT-130 (low dose and high dose). The safety of the low dose was assessed by an independent study monitoring board before testing the high dose. A total of 26 participants have been enrolled in the U.S. Of the 26 participants enrolled, 16 received treatment with AMT-130 (“Treated Group”) and 10 did not receive any study treatment (“Imitation Group”). Participants assigned to the Treated Group received the dose of AMT-130 during a neurosurgical visit. AMT-130 was infused into two specific brain regions (caudate and putamen, together known as the striatum) under general anesthesia at a surgical center that specializes in these procedures. This is done by drilling two to six small holes in the skull and administering AMT-130 by a micro-catheter. For participants assigned to the Imitation Group, small, superficial holes were drilled into the surface of the skull under general anesthesia, but they did NOT receive a dose of AMT-130. 

    The main part of the study lasts for 12–24 months, with additional bi-annual visits out to 5 years total for continued safety follow up. Procedures include clinic visits, assessments of physical and neurological health, a neurosurgical procedure, lumbar punctures, MRI brain scans, and samples of body fluids. The study is double-blinded” meaning neither the patient, the investigator or clinical staff will know if the patient is in the Treated Group or the Imitation Group.

  • What are the possible risks and discomforts?

    This is the first study in humans testing AMT-130 gene therapy. Currently, there is no information on the long-term side effects of AMT-130 in humans. AMT-130 has been studied in animals. The doses in this study are based on doses given to animals and were found to be generally safe. Some AAV vectors have been approved for clinical use and are being used in several gene therapy clinical trials. In general, AAV vectors are considered safe. Risks that should be considered are the following:

    • Treatment with gene therapy is permanent and cannot be removed once administered.
    • AMT-130 lowers both normal and mutant huntingtin protein in animals. The effects of lowering normal and mutant huntingtin protein levels in adults are currently unknown.
    • Patients may be ineligible to receive another gene therapy treatment after receiving AMT-130.
    • Because AMT-130 is investigational, there may be risks or side effects that are not known at this time. There may be rare and unknown side effects, including reactions that may be life threatening.
    • AMT-130 is delivered directly to the brain and will include risks associated with general anesthesia and micro-catheter placement in the brain.
  • Are there any benefits to taking part in this study?

    The goal of this clinical trial is to determine if AMT-130 is safe, and if it can lower huntingtin protein levels and slow the progression of Huntington disease. There may be no therapeutic benefit from participation in this study; however, one may receive benefit from having general medical oversight provided as part of the study protocol. While the individual may not receive any direct benefit, participation in this research study may help others if AMT-130 is found to be safe and effective.

  • Is there an open label extension study for patients randomized into the Imitation Group?

    It is uniQure’s intent to give patients who are randomized into the Imitation Group, and successfully complete the trial out to 12–24 months, the choice to enroll in an open-label extension study in which they are guaranteed to receive AMT-130 (also known as the crossover arm). This can only be done if the independent study monitoring board review all the safety and efficacy data collected up to that point and deem it acceptable to proceed. In order to qualify, the participant will need to be re-screened and meet all inclusion criteria and no exclusion criteria.

  • Where is the study being conducted?

    There are two protocols associated with AMT-130. One of the protocols is based in the US and the other is based in the EU. The specific location of sites can be found at clin​i​cal​tri​als​.gov and/or HDTrialfinder​.org. The trial is listed on both sites.

uniQure looks forward to working closely with the HD community to make progress in developing a treatment for Huntington’s disease.

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